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1.  The research rotation: competency-based structured and novel approach to research training of internal medicine residents 
Background
In the United States, the Accreditation Council of graduate medical education (ACGME) requires all accredited Internal medicine residency training programs to facilitate resident scholarly activities. However, clinical experience and medical education still remain the main focus of graduate medical education in many Internal Medicine (IM) residency-training programs. Left to design the structure, process and outcome evaluation of the ACGME research requirement, residency-training programs are faced with numerous barriers. Many residency programs report having been cited by the ACGME residency review committee in IM for lack of scholarly activity by residents.
Methods
We would like to share our experience at Lincoln Hospital, an affiliate of Weill Medical College Cornell University New York, in designing and implementing a successful structured research curriculum based on ACGME competencies taught during a dedicated "research rotation".
Results
Since the inception of the research rotation in 2004, participation of our residents among scholarly activities has substantially increased. Our residents increasingly believe and appreciate that research is an integral component of residency training and essential for practice of medicine.
Conclusion
Internal medicine residents' outlook in research can be significantly improved using a research curriculum offered through a structured and dedicated research rotation. This is exemplified by the improvement noted in resident satisfaction, their participation in scholarly activities and resident research outcomes since the inception of the research rotation in our internal medicine training program.
doi:10.1186/1472-6920-6-52
PMCID: PMC1630691  PMID: 17044924
2.  Global analysis of gene function in yeast by quantitative phenotypic profiling 
Molecular Systems Biology  2006;2:2006.0001.
We present a method for the global analysis of the function of genes in budding yeast based on hierarchical clustering of the quantitative sensitivity profiles of the 4756 strains with individual homozygous deletion of nonessential genes to a broad range of cytotoxic or cytostatic agents. This method is superior to other global methods of identifying the function of genes involved in the various DNA repair and damage checkpoint pathways as well as other interrogated functions. Analysis of the phenotypic profiles of the 51 diverse treatments places a total of 860 genes of unknown function in clusters with genes of known function. We demonstrate that this can not only identify the function of unknown genes but can also suggest the mechanism of action of the agents used. This method will be useful when used alone and in conjunction with other global approaches to identify gene function in yeast.
doi:10.1038/msb4100043
PMCID: PMC1681475  PMID: 16738548
deletion pool; functional genomics; hierarchical clustering; phenotypic profiling; yeast
3.  Integrating phenotypic and expression profiles to map arsenic-response networks 
Genome Biology  2004;5(12):R95.
By integrating phenotypic and transcriptional profiling and mapping the data onto metabolic and regulatory networks, it was shown that arsenic probably channels sulfur into glutathione for detoxification, leads to indirect oxidative stress by depleting glutathione pools, and alters protein turnover via arsenation of sulfhydryl groups on proteins.
Background
Arsenic is a nonmutagenic carcinogen affecting millions of people. The cellular impact of this metalloid in Saccharomyces cerevisiae was determined by profiling global gene expression and sensitivity phenotypes. These data were then mapped to a metabolic network composed of all known biochemical reactions in yeast, as well as the yeast network of 20,985 protein-protein/protein-DNA interactions.
Results
While the expression data unveiled no significant nodes in the metabolic network, the regulatory network revealed several important nodes as centers of arsenic-induced activity. The highest-scoring proteins included Fhl1, Msn2, Msn4, Yap1, Cad1 (Yap2), Pre1, Hsf1 and Met31. Contrary to the gene-expression analyses, the phenotypic-profiling data mapped to the metabolic network. The two significant metabolic networks unveiled were shikimate, and serine, threonine and glutamate biosynthesis. We also carried out transcriptional profiling of specific deletion strains, confirming that the transcription factors Yap1, Arr1 (Yap8), and Rpn4 strongly mediate the cell's adaptation to arsenic-induced stress but that Cad1 has negligible impact.
Conclusions
By integrating phenotypic and transcriptional profiling and mapping the data onto the metabolic and regulatory networks, we have shown that arsenic is likely to channel sulfur into glutathione for detoxification, leads to indirect oxidative stress by depleting glutathione pools, and alters protein turnover via arsenation of sulfhydryl groups on proteins. Furthermore, we show that phenotypically sensitive pathways are upstream of differentially expressed ones, indicating that transcriptional and phenotypic profiling implicate distinct, but related, pathways.
doi:10.1186/gb-2004-5-12-r95
PMCID: PMC545798  PMID: 15575969
4.  The Saccharomyces cerevisiae Kinesin-related Motor Kar3p Acts at Preanaphase Spindle Poles to Limit the Number and Length of Cytoplasmic Microtubules 
The Journal of Cell Biology  1997;137(2):417-431.
The Saccharomyces cerevisiae kinesin-related motor Kar3p, though known to be required for karyogamy, plays a poorly defined, nonessential role during vegetative growth. We have found evidence suggesting that Kar3p functions to limit the number and length of cytoplasmic microtubules in a cell cycle–specific manner. Deletion of KAR3 leads to a dramatic increase in cytoplasmic microtubules, a phenotype which is most pronounced from START through the onset of anaphase but less so during late anaphase in synchronized cultures. We have immunolocalized HA-tagged Kar3p to the spindle pole body region, and fittingly, Kar3p was not detected by late anaphase. A microtubule depolymerizing activity may be the major vegetative role for Kar3p. Addition of the microtubule polymerization inhibitors nocodazol or benomyl to the medium or deletion of the nonessential α-tubulin TUB3 gene can mostly correct the abnormal microtubule arrays and other growth defects of kar3 mutants, suggesting that these phenotypes result from excessive microtubule polymerization. Microtubule depolymerization may also be the mechanism by which Kar3p acts in opposition to the anaphase B motors Cin8p and Kip1p. A preanaphase spindle collapse phenotype of cin8 kip1 mutants, previously shown to involve Kar3p, is markedly delayed when microtubule depolymerization is inhibited by the tub2-150 mutation. These results suggest that the Kar3p motor may act to regulate the length and number of microtubules in the preanaphase spindle.
PMCID: PMC2139775  PMID: 9128252
5.  ADY1, A Novel Gene Required for Prospore Membrane Formation at Selected Spindle Poles in Saccharomyces cerevisiae 
Molecular Biology of the Cell  2001;12(9):2646-2659.
ADY1 is identified in a genetic screen for genes on chromosome VIII of Saccharomyces cerevisiae that are required for sporulation. ADY1 is not required for meiotic recombination or meiotic chromosome segregation, but it is required for the formation of four spores inside an ascus. In the absence of ADY1, prospore formation is restricted to mainly one or two spindle poles per cell. Moreover, the two spores in the dyads of the ady1 mutant are predominantly nonsisters, suggesting that the proficiency to form prospores is not randomly distributed to the four spindle poles in the ady1 mutant. Interestingly, the meiosis-specific spindle pole body component Mpc54p, which is known to be required for prospore membrane formation, is localized predominantly to only one or two spindle poles per cell in the ady1 mutant. A partially functional Myc-Pfs1p is localized to the nucleus of mononucleate meiotic cells but not to the spindle pole body or prospore membrane. These results suggest that Pfs1p is specifically required for prospore formation at selected spindle poles, most likely by ensuring the functionality of all four spindle pole bodies of a cell during meiosis II.
PMCID: PMC59701  PMID: 11553705

Results 1-5 (5)